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To use a Machine Learning (ML) approach to compare Neuropsychiatric Symptoms (NPS) in participants of a longitudinal study who developed dementia and those who did not.

Design:

Mann-Whitney U and ML analysis. Nine ML algorithms were evaluated using a 10-fold stratified validation procedure. Performance metrics (accuracy, recall, F-1 score, and Cohen’s kappa) were computed for each algorithm, and graphic metrics (ROC and precision-recall curves) and features analysis were computed for the best-performing algorithm.

Setting:

Primary care health centers.

Participants:

128 participants: 78 cognitively unimpaired and 50 with MCI.

Measurements:

Diagnosis at baseline, months from the baseline assessment until the 3rd follow-up or development of dementia, gender, age, Charlson Comorbidity Index, Neuropsychiatric Inventory-Questionnaire (NPI-Q) individual items, NPI-Q total severity, and total stress score and Geriatric Depression Scale-15 items (GDS-15) total score.

Results:

30 participants developed dementia, while 98 did not. Most of the participants who developed dementia were diagnosed at baseline with amnestic multidomain MCI. The Random Forest Plot model provided the metrics that best predicted conversion to dementia (e.g. accuracy=.88, F1=.67, and Cohen’s kappa=.63). The algorithm indicated the importance of the metrics, in the following (decreasing) order: months from first assessment, age, the diagnostic group at baseline, total NPI-Q severity score, total NPI-Q stress score, and GDS-15 total score.

Conclusions:

ML is a valuable technique for detecting the risk of conversion to dementia in MCI patients. Some NPS proxies, including NPI-Q total severity score, NPI-Q total stress score, and GDS-15 total score, were deemed as the most important variables for predicting conversion, adding further support to the hypothesis that some NPS are associated with a higher risk of dementia in MCI.

Vocally disruptive behavior (VDB) is a common and particularly difficult symptom to manage in dementia. VDB is usually considered collectively with agitation and aggression as a component of behavioral and psychological symptoms in dementia and is therefore poorly understood as an individual symptom. A review of the literature is described where VDB as a challenging behavior has been individually examined as a symptom. A case of VDB occurring in patient with dementia is described where the patient’s repetitive vocalizations responded to treatment with pregabalin. This has not been previously reported in the literature. The prevalence of VDB, the factors associated with it and the current management guidelines for clinicians are outlined with a review of the drug treatment strategies for VDB. Pregabalin with its unique pharmacological profile and excellent tolerability should be considered as a possible treatment for VDB where drug treatment is indicated.

Alzheimer's disease and vascular dementia are associated with overlapping symptoms of anxiety and depression. More accurate discrimination between emerging neuropsychiatric and cognitive symptoms would better assist illness detection. The potential for protection against cognitive decline and dementia following early identification and intervention of neuropsychiatric symptoms warrants investigation.

Declaration of interest

B.J.S. consults for Peak, Mundipharma and Cambridge Cognition. J.T.O. has acted as a consultant for TauRx, Axon, GE Healthcare and Lilly.

To estimate the prevalence of Mild Behavioral Impairment (MBI) in people with Subjective Cognitive Decline (SCD), and validate the Mild Behavioral Impairment Checklist (MBI-C) with respect to score distribution, sensitivity, specificity, and utility for MBI diagnosis, as well as correlation with other neuropsychological tests.

An extensive evaluation, including Questionnaire for Subjective Memory Complaints, Mini-Mental State Examination, Cambridge Cognitive Assessment-Revised, Neuropsychiatric Inventory-Questionnaire (NPI-Q), the Geriatric Depression Scale-15 items (GDS-15), the Lawton and Brody Index and the MBI-C, which was administered by phone to participants’ informants.

Results:

MBI prevalence was 5.8% in those with SCD. The total MBI-C scoring was low and differentiated people with MBI at a cut-off point of 8.5 (optimizing sensitivity and specificity). MBI-C total scoring correlated positively with NPI-Q, Questionnaire for Subjective Cognitive Complaints (QSCC) from the informant and GDS-15.

Conclusions:

The phone administration of the MBI-C is useful for detecting MBI in people with SCD. The prevalence of MBI in SCD was low. The MBI-C detected subtle Neuropsychiatric symptoms (NPS) that were correlated with scores on the NPI-Q, depressive symptomatology (GDS-15), and memory performance perceived by their relatives (QSCC). Next steps are to determine the predictive utility of MBI in SCD, and its relation to incident cognitive decline over time.

Neuropsychiatric symptoms (NPI) of dementia are important determinants of caregiver burden, while caregiver coping styles and competences can relieve burden. Caregivers differ in coping with the demands made on them and in experienced burden. What changes in caregivers explain recovery from burden, and which caregiver characteristics predict recovery from burden over time, and does treatment make a difference?

Methods:

This study into recovery from burden was a secondary analysis of data collected in a formerly conducted randomized controlled trial (RCT) on the integrated reactivation and rehabilitation (IRR) programme in a psychiatric-skilled nursing home, compared to usual care (UC; i.e. day care, assisted living arrangements, and nursing home wards). For this secondary analysis, longitudinal data on persons with dementia and caregivers were used from baseline (T1), end of treatment (T2), and at nine months (T3).

Results:

Caregivers with an improved sense of competence (SCS) who care for persons with dementia with a decreased severity of NPI have the highest chance of recovering from burden (CSI). Caregivers with a tendency to feel involved with others and sympathize with others (affiliation, ICL-R) have a slightly lower probability of improvement with respect to their sense of competence in the short term. The number of improved caregivers was higher in IRR than UC.

Conclusion:

Recovery depends on both an improved sense of competence and a decreased severity of NPI. Combined interventions that address both NPI and focus on enhancing caregiver's sense of competence have added value when it comes to decreasing caregiver burden.

Current policy emphasises the importance of ‘living well’ with dementia, but there has been no comprehensive synthesis of the factors related to quality of life (QoL), subjective well-being or life satisfaction in people with dementia. We examined the available evidence in a systematic review and meta-analysis. We searched electronic databases until 7 January 2016 for observational studies investigating factors associated with QoL, well-being and life satisfaction in people with dementia. Articles had to provide quantitative data and include ⩾75% people with dementia of any type or severity. We included 198 QoL studies taken from 272 articles in the meta-analysis. The analysis focused on 43 factors with sufficient data, relating to 37639 people with dementia. Generally, these factors were significantly associated with QoL, but effect sizes were often small (0.1–0.29) or negligible (<0.09). Factors reflecting relationships, social engagement and functional ability were associated with better QoL. Factors indicative of poorer physical and mental health (including depression and other neuropsychiatric symptoms) and poorer carer well-being were associated with poorer QoL. Longitudinal evidence about predictors of QoL was limited. There was a considerable between-study heterogeneity. The pattern of numerous predominantly small associations with QoL suggests a need to reconsider approaches to understanding and assessing living well with dementia.

The accurate clinical characterisation of mild cognitive impairment (MCI) is becoming increasingly important. The aim of this study was to compare the neuropsychiatric symptoms and cognitive profile of MCI with Lewy bodies (MCI-LB) with Alzheimer's disease MCI (MCI-AD).

Methods

Participants were ⩾60 years old with MCI. Each had a thorough clinical and neuropsychological assessment and 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane single photon emission computed tomography FP-CIT SPECT). MCI-LB was diagnosed if two or more diagnostic features of dementia with Lewy bodies were present (visual hallucinations, cognitive fluctuations, motor parkinsonism, rapid eye movement sleep behaviour disorder or positive FP-CIT SPECT). A Lewy body Neuropsychiatric Supportive Symptom Count (LBNSSC) was calculated based on the presence or absence of the supportive neuropsychiatric symptoms defined by the 2017 DLB diagnostic criteria: non-visual hallucinations, delusions, anxiety, depression and apathy.

MCI-LB is associated with neuropsychiatric symptoms and a cognitive profile similar to established DLB. This supports the concept of identifying MCI-LB based on the presence of core diagnostic features of DLB and abnormal FP-CIT SPECT imaging. The presence of supportive neuropsychiatric clinical features identified in the 2017 DLB diagnostic criteria was helpful in differentiating between MCI-LB and MCI-AD.

Lewy body dementia (consisting of dementia with Lewy bodies and Parkinson's disease dementia) is a common neurodegenerative disease characterised by visual hallucinations, fluctuating attention, motor disturbances, falls, and sensitivity to antipsychotics. This combination of features presents challenges for pharmacological management. Given this, we sought to review evidence for non-pharmacological interventions with patients with Lewy body dementia and their carers. Bibliographic databases were searched using a wide range of search terms and no restrictions were placed on study design, language, or clinical setting. Two reviewers independently assessed papers for inclusion, rated study quality, and extracted data. The search identified 21 studies including two randomised controlled trials with available subgroup data, seven case series, and 12 case studies. Most studies reported beneficial effects of the interventions used, though the only sizeable study was on dysphagia, showing a benefit of honey-thickened liquids. Given the heterogeneity of interventions and poor quality of the studies overall, no quantitative synthesis was possible. Overall, identified studies suggested possible benefits of non-pharmacological interventions in Lewy body dementia, but the small sample sizes and low quality of studies mean no definite recommendations can be offered. Our findings underscore the clear and urgent need for future research on this topic.

Behavioral and psychological symptoms of dementia (BPSD) are a primary manifestation of brain dysfunction in dementia and a great challenge in caregiving. While BPSD are historically associated with caregiver distress, it is unclear whether there is an identifiable point where BPSD number is associated with heightened caregiver distress. The purpose of this study was to determine if such a tipping point exists to assist clinicians in identifying caregiver compromise.

Methods:

Analyses were performed with three datasets totaling 569 community-dwelling persons with dementia and their caregivers. Each included identical demographic, BPSD, cognitive, and caregiver well-being measures. Linear regression was performed with 16 BPSD symptoms on caregiver well-being measures and predictive values determined with receiver operating characteristic (ROC) curves and pre-defined scores for clinically significant distress.

Caring for persons with four or more BPSD appears to reflect a tipping point for clinically meaningful distress. Findings have implications for clinicians working with persons with dementia and their caregivers and suggest need for continuous monitoring of BPSD and identification of at risk caregivers.

We apply recently recommended Parkinson's disease mild cognitive impairment (PD-MCI) classification criteria from the movement disorders society (MDS) to PD patients and controls and compare diagnoses to that of short global cognitive scales at baseline and over time. We also examine baseline prevalence of neuropsychiatric symptoms across different definitions of MCI.

We confirmed that PD-MCI (a) is frequent, (b) increases the risk of PDD, and (c) affects multiple cognitive domains. We highlight the predictive variability of different criteria, suggesting the need for further refinement and standardization. When a common dementia outcome was used, the Level II MDS optimal testing battery with impairment defined as two SD below norms in 2+ tests performs the best. Neuropsychiatric symptoms were more common in PD across all baseline and longitudinal cognitive classifications.

Conclusions:

Our results advance previous findings on the utility of MDS PD-MCI criteria for PD patients and controls at baseline and over time. Additionally, we emphasize the possible utility of other cognitive scales and neuropsychiatric symptoms.

Mild behavioral impairment (MBI) is characterized by later life acquired, sustained, and impactful neuropsychiatric symptoms (NPS) of any severity that cannot be better accounted for by other formal medical and psychiatric nosology. MBI is an “at risk” state for incident cognitive decline and dementia, and for some, MBI is the index manifestation of neurodegeneration, observed in advance of cognitive impairment. Initially described in Frontotemporal Dementia (FTD), MBI evolved to describe a preclinical stage of all cause dementia, and has been operationalized in the International Society to Advance Alzheimer's Research and Treatment-Alzheimer's Association (ISTAART-AA) proposed research diagnostic criteria. Here, we describe three cases in which patients diagnosed with a variety of dementing conditions initially presented with NPS to the Cognitive Neurosciences Clinic at the University of Calgary, Canada. All patients described in our series were given a final diagnosis of dementia; the etiology supported by clinical, cognitive, and neuroimaging findings. In all three cases, the progression to dementia was preceded by NPS that meet criteria for MBI. With these examples, we are able to illustrate that MBI can represent a premonitory stage of dementia of different etiologies. These cases demonstrate early use of the MBI checklist (MBI-C). The cases presented in this series serve as examples of NPS as early manifestations of dementia. Our case examples include both FTD and AD, and demonstrate that before a diagnosis of a neurodegenerative disease is considered, often patients will be diagnosed with and treated for a psychiatric condition. These early NPS can be characterized within the domains outlined in the ISTAART-AA MBI criteria, and detected with the MBI-C, which may help clinicians consider neurodegenerative disease in the differential diagnosis of later life onset psychiatric symptomatology.

We aimed to assess whether there were any changes in the use of psychotropic drugs in Norwegian nursing homes between 2004 and 2011. Also, we investigated whether the predictors of use of specific psychotropic drug groups have changed.

Methods:

We conducted a secondary analysis of two cohort studies of two Norwegian nursing home samples (2004/05 and 2010/11). Multivariate models were applied.

Results:

We found a significant decrease in the prescription of antipsychotic drugs between 2004 and 2011 (0.63 OR, 95%CI = 0.49–0.82, p < 0.001) even after adjusting for relevant demographic and clinical variables. There are only minor changes for the other psychotropic drugs. We found that (1) the use of specific psychotropic drug groups as well as the number of psychotropic drugs used was associated with more affective symptoms and (2) the use of specific psychotropic drug groups as well as the number of psychotropic drugs used was associated with lower scores on the Physical Self-Maintenance scale.

Conclusion:

This is the first study to show a robust decrease in antipsychotic drug use in nursing home patients with dementia unrelated to possible changes in case mix. The change might be explained by treatment recommendations against its use except in the most severe conditions of aggression or psychosis. Our findings indicate that it takes several years to implement scientific knowledge in clinical practice in nursing homes.

A dearth of population-based epidemiological research examines neuropsychiatric symptom (NPS) in sub-clinical populations across the spectrum from normal aging to mild cognitive impairment (MCI). The construct of mild behavioral impairment (MBI) describes the emergence of sustained and impactful NPS in advance of or in combination with MCI. This is the first epidemiological study to operationalize the recently published diagnostic criteria for MBI and determine prevalence estimates across the spectrum from cognitively normal to MCI.

This study presents the first population-based prevalence estimates for MBI using the recently published ISTAART-AA diagnostic criteria. Findings indicate relatively high prevalence of MBI in pre-dementia clinical states and amongst cognitively healthy older adults. Findings were gender-specific, with MBI affecting more men than women. Knowing the estimates of these symptoms in the population is essential for understanding and differentiating the very early development of clinical disorders.

We studied the patient and non-patients factors of inappropriate psychotropic drug (PD) prescription for neuropsychiatric symptoms (NPS) in nursing home patients with severe dementia.

Methods:

In a cross-sectional study, the appropriateness of prescriptions was explored using the Appropriate Psychotropic drug use In Dementia (APID) index sum score. This index assesses information from medical records on indication, evaluation, dosage, drug–drug interactions, drug–disease interactions, duplications, and therapy duration. Various measurements were carried out to identify the possible patient and non-patient factors. Linear multilevel regression analysis was used to identify factors that are associated with APID index sum scores. Analyses were performed for groups of PDs separately, i.e. antipsychotics, antidepressants, anxiolytics, and hypnotics.

Results:

The sample consisted of 338 patients with a PD prescription that used 147 antipsychotics, 167 antidepressants, 85 anxiolytics, and 76 hypnotics. It was found that older patients and more severe aggression, agitation, apathy, and depression were associated with more appropriate prescriptions. Additionally, less appropriate prescriptions were found to be associated with more severe anxiety, dementia diagnoses other than Alzheimer dementia, more physician time available per patient, more patients per physician, more years of experience of the physician, and higher nurse's workload.

Conclusions:

The association of more pronounced NPS with more appropriate PD prescriptions implies that physicians should pay more attention to the appropriateness of PD prescriptions when NPS are less manifest. Non-patient-related factors are also associated with the appropriateness of PD prescriptions. However, especially considering that some of these findings are counter-intuitive, more research on the topic is recommended.

Affective and emotional symptoms such as depression, anxiety, euphoria, and irritability are common neuropsychiatric symptoms (NPS) in pre-dementia and cognitively normal older adults. They comprise a domain of Mild Behavioral Impairment (MBI), which describes their emergence in later life as an at-risk state for cognitive decline and dementia, and as a potential manifestation of prodromal dementia. This selective scoping review explores the epidemiology and neurobiological links between affective and emotional symptoms, and incident cognitive decline, focusing on recent literature in this expanding field of research.

Affective and emotional dysregulation are common in preclinical and prodromal dementia syndromes, often being harbingers of neurodegenerative change and progressive cognitive decline. Nosological constraints in distinguishing between pre-existing psychiatric symptomatology and later life acquired NPS limit historical data utility, but emerging research emphasizes the importance of addressing time frames between symptom onset and cognitive decline, and age of symptom onset.

Conclusion:

Affective symptoms are of prognostic utility, but interventions to prevent dementia syndromes are limited. Trials need to assess interventions targeting known dementia pathology, toward novel pathology, as well as using psychiatric medications. Research focusing explicitly on later life onset symptomatology will improve our understanding of the neurobiology of NPS and neurodegeneration, enrich the study sample, and inform observational and clinical trial design for prevention and treatment strategies.

To investigate the differential associations between sensory loss and neuropsychiatric symptoms among older adults with and without diagnosed neurocognitive disorder.

Methods:

The sample comprised 1,393 adults (52.3% men) aged between 72 and 79 years from a community-based cohort study. There were 213 cases of mild and 64 cases of major neurocognitive disorders. The main outcome was number of informant reported symptoms on the Neuropsychiatric Inventory (NPI). Sensory loss was defined by visual acuity worse the 0.3 logMAR (6/12 or 20/40) and self-reported hearing problems.

Results:

Clinically relevant NPI symptoms were reported in 182 (13.1%) participants, but no individual symptom occurred in more than 5% of the total sample. Among participants diagnosed with a major neurocognitive disorder, those with any sensory loss had over three times (95%CI: 1.72–11.78) greater rates of NPI symptoms than those with unimpaired levels of sensory functioning. There were no differences in the number of neuropsychiatric symptoms by type of sensory loss, and no additional risk associated with a dual sensory loss compared to a single sensory loss. There was no evidence of an association between sensory loss and number of neuropsychiatric symptoms among cognitively healthy adults.

Conclusions:

The extent to which this association is the result of underlying neuropathology, unmet need, or interpersonal factors is unclear. These findings have significant implications for dementia care settings, including hospitals and respite care, as patients with sensory loss are at increased risk of neuropsychiatric symptoms and may require additional psychosocial support. Interventions to manage sensory loss and reduce the impact of sensory limitations on neuropsychiatric symptoms are needed.

Psychotropic medications are widely prescribed to manage neuropsychiatric symptoms (NPS) of Alzheimer's disease (AD). Our objective was to investigate the longitudinal associations between psychotropic medication use and NPS, cognition, and functional performance in persons with very mild or mild AD at baseline.

Methods:

Data were collected as part of the prospective three-year study of home-dwelling persons with AD and their caregivers (n = 236 dyads). The associations between psychotropic medication use and clinical measures were analyzed using repeated measures Generalized Estimating Equation (GEE) models. NPS, cognition, daily functioning, and disease severity were assessed with NPI, CERAD-NB, or MMSE, ADCS-ADL, and CDR-SOB, respectively. All analyses were adjusted for age, gender, education, and co-morbidities.

Results:

The prevalence of benzodiazepines and related medications increased from 16% to 24% (p = 0.031), antidepressants from 11% to 18% (p = 0.057), and antipsychotics from 4% to 16% (p = 0.011) in the three years following AD diagnosis. In adjusted multivariable analyses, a one-point increase in NPI increased the odds of using any psychotropic medication class by 4% (odds ratio (OR) 1.04, 95% confidence interval (CI) 1.01–1.07). ADCS-ADL (1/OR 1.04, 95% CI 1.02–1.06) and CDR-SOB (OR 1.27, 95% CI 1.13–1.42) were associated with use of antipsychotics. CERAD-NB and MMSE were not associated with any psychotropic medication class use in the models.

Conclusions:

Psychotropic medication use increased significantly in relation to increasing dependency in AD, especially with NPS. Furthermore, the use of antipsychotics increased with disease severity, and with decline in daily functioning. Cognitive performance was not associated with psychotropic medication use.

This study assessed the prevalence and factor structure of behavioral and psychological symptoms of dementia (BPSD) in a community-based sample of older adults with dementia and identified their correlates.

Methods:

Data collected from 399 Singapore residents with dementia aged 60 years and above, interviewed along with a family/friend during a national survey, were used for this analysis. Neuropsychiatric Inventory Questionnaire assessed older adults’ BPSD. Other data included socio-demographics, dementia severity, cognition, chronic physical conditions, disability, and caregivers’ burden. Exploratory factor analysis assessed BPSD sub-groups, factor scores of which were used to identify socio-demographic, and clinical correlates.

Results:

Prevalence of BPSD was 67.9% and 30% of the population had experienced three or more BPSD in the past month. Two distinct and moderately correlated symptom groups representing “psychosis and behavior dysregulation” and “mood disturbance and restlessness” were identified. As factor scores for both the groups increased with older age, poor cognition and caregiver burden, the former was also related to being never married and having no formal education.

Conclusions:

Study provides evidence of two distinct groups of BPSD and their important correlates. Clinicians treating BPSD should consider their age and cognitive impairment and be cognizant of their caregivers’ burden.

Dementia is a neurodegenerative syndrome that interferes with multiple aspects of life, including cognition, daily functioning, and behavior. Despite the large heterogeneity in symptom development, these three domains are seldom studied simultaneously. This study investigates how trajectories of these domains are interrelated within individuals over time, and how they in turn are related to dementia severity and quality of life (QoL).

Methods:

We used data from a longitudinal clinical cohort study, including 331 dementia patients. Cognitive status was measured using the Mini-Mental State Examination, daily functioning was measured with the disability assessment for dementia and neuropsychiatric symptoms (NPS) were scored using the neuropsychiatric inventory. We investigated the relationships in the time course of the various dementia domains using random effects multilevel models and parallel-process growth models.

Results:

Changes in cognition and daily functioning were highly correlated over time (r = 0.85, p < 0.01), as were changes in NPS and functioning (r = −0.60, p < 0.01), while changes in cognition and NPS were not (r = −0.20, p = 0.06). All three domains were strongly associated with dementia severity over time (p < 0.01). Decreased functioning and increased NPS were both associated with decreased QoL (β = 2.97, p < 0.01 and β = −2.41, p < 0.01, respectively), while cognition was not (β = 0.01, p = 0.93).

Conclusion:

This study demonstrates the heterogeneity of dementia progression between individuals and between different dementia domains within individuals. To improve our understanding of dementia progression, future research should embrace a broader perspective encompassing multiple outcome measures along with the patient's profile, including neurological factors as well as physical, social, and psychiatric health.

Behavioral and psychological symptoms in dementia (BPSD) are important predictors of institutionalization as well as caregiver burden and depression. Previous reviews have tended to group BPSD as one category with little focus on the role of the individual symptoms. This review investigates the role of the individual symptoms of BPSD in relation to the impact on different measures of family caregiver well-being.

Methods:

Systematic review and meta-analysis of papers published in English between 1980 and December 2015 reporting which BPSD affect caregiver well-being. Paper quality was appraised using the Downs and Black Checklist (1998).

Results:

Forty medium and high quality quantitative papers met the inclusion criteria, 16 were suitable to be included in a meta-analysis of mean distress scores. Depressive behaviors were the most distressing for caregivers followed by agitation/aggression and apathy. Euphoria was the least distressing. Correlation coefficients between mean total behavior scores and mean distress scores were pooled for four studies. Irritability, aberrant motor behavior and delusions were the most strongly correlated to distress, disinhibition was the least correlated.

Conclusions:

The evidence is not conclusive as to whether some BPSD impact caregiver well-being more than others. Studies which validly examined BPSD individually were limited, and the included studies used numerous measures of BPSD and numerous measures of caregiver well-being. Future research may benefit from a consistent measure of BPSD, examining BPSD individually, and by examining the causal mechanisms by which BPSD impact well-being by including caregiver variables so that interventions can be designed to target BPSD more effectively.